Carcinoma of the esophagus is a disease that has poor overall prognosis, with 1-year and 5-year survival rates of approximately 18% and 6%, respectively. The diagnosis of esophageal carcinoma is usually obtained using endoscopy with biopsy and brush cytology. Once the diagnosis is established, the patient typically undergoes clinical staging to determine the depth of penetration of the lesion and to determine the extent of lymph node metastasis. If there are no signs of tumor penetration beyond the esophageal wall and no signs of lymph node involvement, the patient should be considered potentially curable and undergo surgical resection. On the other hand, if there is involvement of lymph nodes or penetration beyond the esophageal wall, treatment alternatives such as radiotherapy and chemotherapy may take place, possibly followed by an attempt at surgical resection. Thus, staging is critical in determined a course of treatment.
Endoscopic ultrasound (EUS) is a relatively recent imaging modality that is being successfully used in tumor staging of esophageal carcinoma. It combines the proximity to the gastrointestinal (GI) wall provided by endoscopic imaging with the detailed morphological information provided by ultrasound imaging.
Tumor staging using EUS is done through the well known TNM classification system, which classifies esophageal carcinoma using stages of the primary tumor, regional lymph node involvement, and distant metastasis. Since 1987, clinical staging of esophageal carcinoma has been done according to this TNM system. In the TNM system, the evaluation of the primary tumor (T stage) only considers depth of penetration into the esophageal wall. Anatomic location and length of tumor are no longer considered relevant. Evaluation of regional lymph nodes (N stage) is based solely on the presence or absence of metastatic carcinoma. Anatomic site once again is no longer of importance. Distant metastasis (M stage) indicates involvement of tissues outside of the immediate area of the primary tumor including celiac axis lymph nodes. As known to those skilled in the art, in the TNM system the stages for regional lymph nodes are as follows: NX indicates that regional lymph nodes cannot be assessed, N0 indicates that no regional lymph node metastasis was detected, and N1 indicates that regional lymph node metastasis was detected.
It is generally accepted that EUS is most accurate at determining T stage, which is the depth of penetration through the esophageal wall. The performance of EUS at T staging is regarded as being superior to that of computed tomography (CT). Because of many factors, not the least of which is the subjective nature of prior art methods of using EUS to determine lymph node involvement, EUS is considered to be somewhat less accurate at determining N stage, which reflects the status of regional lymph nodes. The overall accuracy in determining N stage is in the range of 70-80%. This accuracy, however, is achieved based on N staging of cases (patients), rather than N staging of individual lymph nodes, which is preferable. There is little understanding about the changes that may occur to sonographic characteristics of lymph nodes once they are affected by tumor. Additionally, the established EUS criteria for evaluating lymph nodes have not been rigorously evaluated. Nevertheless, the performance of EUS in N staging is still generally considered to be more reliable than that of CT and MRI. Finally, EUS is considered to be inappropriate for assessment of M stage, which is related to distant metastasis, because common sites such as the liver and the celiac axis are not properly observed with the endoscope; most of the liver is not well seen, and the celiac axis is not appreciated in every case.
The importance of staging in general, and N staging in particular, is better understood when considering that only depth of tumor penetration and lymph node status have major impact on patient survival rate. Studies have shown that factors that affected patient prognosis included: the depth of penetration of the tumor through the esophageal wall and the presence of lymph node involvement. Thus, clinical N staging plays a relevant role in predicting prognosis. A variety of treatments such as surgical resection, radiotherapy, chemotherapy, or any combination thereof can be used in cases of esophageal carcinoma; however, the selection of treatment is directed to a large degree by the TNM stage of the carcinoma. Accurate clinical staging, therefore, is an important guide in determining therapy for those with esophageal carcinoma.
As important as EUS staging of regional lymph nodes is, there are several important problems with prior art methods of determining N stage using EUS. First of all, EUS characteristics are evaluated qualitatively; their measures essentially reflect what the endoscopists can see on the EUS display or printout. Thus, EUS staging determinations are clearly dependent on the perception of the observer, being subject to both intra- and interobserver variabilities.
Moreover, there is a lot of controversy regarding which node features are predictive of N stage. The strategy for N staging using EUS is not standardized. There is no consensus if size alone is a good predictor of lymph node malignancy. Emphasis on lymph node characteristics such as echopattern, size, and shape may vary among individual endoscopists. One criterion often used is that lymph nodes larger than one centimeter are considered to be malignant. Also, there is a trend among different investigators to consider round and hypoechoic (dark) nodes as malignant, and ellipsoid and hyperechoic (bright) nodes as benign. Regular borders (little jaggedness) is an EUS characteristic often attributed to malignant nodes. Again, these characteristics are heavily dependent on what the endoscopist sees. The only measurements that can be labeled quantitative to a certain degree is size, and in some studies, circularity. Both measurements take advantage of the capability provided by EUS equipment which allows the measurement of dimension along a line placed by the operator on the display monitor. Size is then measured as the maximum length within lymph node borders. When measured, circularity is obtained by the ratio of the maximum length to the length perpendicular to it. Still, even these seemingly more quantitative measurements are highly dependent on the observer. Even more importantly, very little evidence exists establishing that some or any of these perceived criteria are actually indicators of the presence or absence of lymph node metastasis.
Thus, there is a need for a quantitative system and method for determining involvement of regional lymph nodes using endoscopic ultrasound in staging esophageal carcinoma.